2-205745778-T-G

Variant names:

• chr2-205745778-T-G
• rs849563
• NM_003872.3:c.1674T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003872.3(NRP2):​c.1674T>G​(p.Pro558Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,614,010 control chromosomes in the GnomAD database, including 23,123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2375 hom., cov: 33)
  • Exomes 𝑓: 0.16 (20748 hom.)
• Consequence: NRP2 NM_003872.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.57
• Publications: 24 publications found

Genes affected

NRP2 (HGNC:8005): (neuropilin 2) This gene encodes a member of the neuropilin family of receptor proteins. The encoded transmembrane protein binds to SEMA3C protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3C} and SEMA3F protein {sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3F}, and interacts with vascular endothelial growth factor (VEGF). This protein may play a role in cardiovascular development, axon guidance, and tumorigenesis. This protein has also been determined to act as a co-receptor for SARS-CoV-2 (which causes COVID-19) to infect host cells. [provided by RefSeq, Jul 2021]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-205745778-T-G is Benign according to our data. Variant chr2-205745778-T-G is described in ClinVar as Benign. ClinVar VariationId is 3060291.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.57 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRP2	NM_003872.3	c.1674T>G	p.Pro558Pro	synonymous_variant	Exon 10 of 17	ENST00000357785.10	NP_003863.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRP2	ENST00000357785.10	c.1674T>G	p.Pro558Pro	synonymous_variant	Exon 10 of 17	1	NM_003872.3	ENSP00000350432.5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25543 AN: 152166 Hom.: 2368 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.188 AC: 47120 AN: 251174 AF XY: 0.186

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.166

GnomAD4 exome AF: 0.156 AC: 227626 AN: 1461726 Hom.: 20748 Cov.: 34 AF XY: 0.158 AC XY: 114672 AN XY: 727160

African (AFR) AF: 0.192 AC: 6422 AN: 33478

American (AMR) AF: 0.228 AC: 10183 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4137 AN: 26136

East Asian (EAS) AF: 0.475 AC: 18859 AN: 39694

South Asian (SAS) AF: 0.226 AC: 19507 AN: 86242

European-Finnish (FIN) AF: 0.131 AC: 7004 AN: 53406

Middle Eastern (MID) AF: 0.147 AC: 846 AN: 5766

European-Non Finnish (NFE) AF: 0.135 AC: 150531 AN: 1111916

Other (OTH) AF: 0.168 AC: 10137 AN: 60384

GnomAD4 genome AF: 0.168 AC: 25570 AN: 152284 Hom.: 2375 Cov.: 33 AF XY: 0.170 AC XY: 12630 AN XY: 74464

African (AFR) AF: 0.187 AC: 7788 AN: 41560

American (AMR) AF: 0.181 AC: 2770 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3468

East Asian (EAS) AF: 0.453 AC: 2343 AN: 5168

South Asian (SAS) AF: 0.234 AC: 1131 AN: 4826

European-Finnish (FIN) AF: 0.126 AC: 1340 AN: 10618

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9195 AN: 68018

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.140 Hom.: 2455

Bravo AF: 0.175

Asia WGS AF: 0.322 AC: 1118 AN: 3478

EpiCase AF: 0.133

EpiControl AF: 0.135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

NRP2-related disorder Benign:1

Aug 19, 2022

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.34
DANN	Benign	0.59
PhyloP100		-1.6
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs849563; hg19: chr2-206610502; COSMIC: COSV55928683; COSMIC: COSV55928683;